SBIR Phase II: Anaerobic Biomanufacturing of 3-Hydroxypropionic Acid Utilizing Whole-Kernel Corn Feedstock

The broader/commercial impact of this Small Business Innovation Research (SBIR) Phase II project will be the establishment of a cost-effective, domestic biomanufacturing platform for producing key chemical ingredients from alternate sources. This innovation addresses the national need for more resilient supply chains by reducing reliance on foreign chemical production. The technology is designed to repurpose existing bioethanol production infrastructure, providing a pathway to revitalize these assets and support economic development and job creation in rural agricultural communities. By creating a sustainable, bio-based alternative for chemicals used in countless consumer products, from personal care items to paints and coatings, this project will deliver significant economic and societal benefits. The focus of this project is a chemical intermediate that serves as a feedstock used to manufacture a wide range of acrylic-based materials. Furthermore, the project will advance scientific and technological understanding by demonstrating a new, more energy-efficient method for engineering microorganisms to produce valuable chemicals without the need for oxygen, a long-standing challenge in the field of industrial biotechnology. The proposed project addresses the key technical and economic barriers that have historically limited the anaerobic, or oxygen-free, bio-production of valuable organic acids. The primary challenge is the large amount of cellular energy required to produce and export these acids from the microbial cell, which makes the process inefficient. The research objective is to develop a highly optimized yeast strain capable of producing 3-hydroxypropionic acid (3-HP) efficiently under anaerobic conditions. The research plan involves integrating several advanced genetic modifications into a single production strain. These modifications are designed to improve the yeast’s energy efficiency, including the incorporation of novel cellular pumps for moving protons and the 3-HP product, optimizing pathways to generate more energy, and rebalancing the cell’s internal chemistry. The anticipated technical result is a robust production strain that achieves specific performance targets for yield, concentration, and production rate, proving the commercial viability of the anaerobic process. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.